Involvement of phosphatase and tensin homolog deleted from chromosome 10 in rodent model of neuropathic pain

Shi Ying Huang, Chun Sung Sung, Wu Fu Chen, Chun Hong Chen, Chien Wei Feng, San Nan Yang, Han Chun Hung, Nan Fu Chen, Pey Ru Lin, San Cher Chen, Hui Min David Wang, Tian Huei Chu, Ming Hong Tai, Zhi Hong Wen*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

29 Scopus citations

Abstract

Background: Many cancer research studies have extensively examined the phosphatase and tensin homolog deleted from chromosome 10 (PTEN) pathway. There are only few reports that suggest that PTEN might affect pain; however, there is still a lack of evidence to show the role of PTEN for modulating pain. Here, we report a role for PTEN in a rodent model of neuropathic pain. Results: We found that chronic constriction injury (CCI) surgery in rats could elicit downregulation of spinal PTEN as well as upregulation of phosphorylated PTEN (phospho-PTEN) and phosphorylated mammalian target of rapamycin (phospho-mTOR). After examining such changes in endogenous PTEN in neuropathic rats, we explored the effects of modulating the spinal PTEN pathway on nociceptive behaviors. The normal rats exhibited mechanical allodynia after intrathecal (i.t.) injection of adenovirus-mediated PTEN antisense oligonucleotide (Ad-antisense PTEN). These data indicate the importance of downregulation of spinal PTEN for nociception. Moreover, upregulation of spinal PTEN by i.t. adenovirus-mediated PTEN (Ad-PTEN) significantly prevented CCI-induced development of nociceptive sensitization, thermal hyperalgesia, mechanical allodynia, cold allodynia, and weight-bearing deficits in neuropathic rats. Furthermore, upregulation of spinal PTEN by i.t. Ad-PTEN significantly attenuated CCI-induced microglia and astrocyte activation, upregulation of tumor necrosis factor-α (TNF-α) and phospho-mTOR, and downregulation of PTEN in neuropathic rats 14 days post injury. Conclusions: These findings demonstrate that PTEN plays a key, beneficial role in a rodent model of neuropathic pain.

Original languageEnglish
Article number59
JournalJournal of Neuroinflammation
Volume12
Issue number1
DOIs
StatePublished - 26 03 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© Huang et al.

Keywords

  • Astrocyte
  • Chronic constriction injury
  • Intrathecal
  • Neuroinflammation

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